2,5-二甲基-4-甲氧基吡啶氮氧化物 | 116419-03-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2,5-二甲基-4-甲氧基吡啶氮氧化物
• 英文名称: 2,5-dimethyl-4-methoxypyridine 1-oxide
• 英文别名: 4-methoxy-2,5-dimethylpyridine 1-oxide；4-methoxy-2,5-dimethyl-1-oxidopyridin-1-ium
• CAS: 116419-03-5
• 化学式: C₈H₁₁NO₂
• 分子量: 153.181
• InChiKey: CCIQWCWHFYTLPA-UHFFFAOYSA-N

物化性质

• 沸点：
  325.9±37.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  34.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,5-二甲基-4-甲氧基吡啶氮氧化物 在 三氯化磷 作用下， 以 氯仿 为溶剂， 以94%的产率得到4-甲氧基-2,5-二甲基吡啶
  参考文献：
  名称：

  Toward the Design of an RNA:DNA Hybrid Binding Agent

  摘要：

  One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA: DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.

  DOI：

  10.1021/ja00085a002
• 作为产物：
  描述：

  2,5-二甲基吡啶 1-氧化物 在 硫酸 、 硝酸 、 乙酰氯 作用下， 以 甲醇 为溶剂， 反应 7.5h， 生成 2,5-二甲基-4-甲氧基吡啶氮氧化物
  参考文献：
  名称：

  Toward the Design of an RNA:DNA Hybrid Binding Agent

  摘要：

  One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA: DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.

  DOI：

  10.1021/ja00085a002

文献信息

• Tricyclic imidazole derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US04634710A1

  公开（公告）日：1987-01-06

  Tricyclic imidazole derivatives of formula I ##STR1## wherein one of R.sup.1 and R.sup.3 is lower alkyl and the other is hydrogen or lower alkyl, R.sup.2 is lower alkyl, n is the number 0 or 1, A is ##STR2## R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each is lower alkyl and R.sup.8 is hydrogen or lower alkyl, and their acid addition salts are described. These compounds are useful as agents for control or prevention of ulcers and of increased gastric acid secretion.

  公式I的三环咪唑衍生物，其中R.sup.1和R.sup.3中的一个是较低的烷基，另一个是氢或较低的烷基，R.sup.2是较低的烷基，n是数字0或1，A是R.sup.4，R.sup.5，R.sup.6和R.sup.7各自是较低的烷基，R.sup.8是氢或较低的烷基，描述了它们的酸盐。这些化合物可用作控制或预防溃疡和胃酸分泌增加的药剂。
• (H+, K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate
  作者：Bernhard Kohl、Ernst Sturm、Joerg Senn-Bilfinger、W. Alexander Simon、Uwe Krueger、Hartmann Schaefer、Georg Rainer、Volker Figala、Kurt Klemm

  DOI：10.1021/jm00084a010

  日期：1992.3

  [(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to

  [（吡啶基甲基）亚磺酰基]苯并咪唑1（PSBs）是一类高度有效的抗分泌（H +，K +）-ATPase抑制剂，需要通过酸激活才能形成其活性成分，即环亚磺酰胺4。（H + ，K +）-ATPase在体内仅在低pH时会产生非选择性的亲硫基4，从而避免了与体内其他巯基的相互作用。进行酸催化转化的倾向取决于2形成中所涉及的官能团的亲核/亲电性质，因为该步骤既决定速率又取决于pH。这项研究的目的是鉴定在具有酸性pH值的刺激胃腺中具有高（H +，K +）-ATPase抑制活性的化合物，但在体外pH值（Na +，K +）-ATPase抑制活性。仔细研究了所有衍生物中存在的吡啶4-甲氧基取代基侧面的取代基的关键影响。3-甲氧基的引入使得抑制剂具有与奥美拉唑和兰索拉唑相似的高效力组合，但是增加了稳定性。这些研究的结果是，化合物1a（INN top托拉唑）被选作候选药物，目前正在进行III期临床研究。
• US4634710A
  申请人：——

  公开号：US4634710A

  公开（公告）日：1987-01-06
• US4981861A
  申请人：——

  公开号：US4981861A

  公开（公告）日：1991-01-01
• Toward the Design of an RNA:DNA Hybrid Binding Agent
  作者：Wenhua Chu、Shigehiro Kamitori、Miho Shinomiya、Robert G. Carlson、Fusao Takusagawa

  DOI：10.1021/ja00085a002

  日期：1994.3

  One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA: DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.